Direct Medical Costs of Venous Thromboembolism and Subsequent Hospital Readmission Rates: An Administrative Claims Analysis From 30 Managed Care Organizations

BACKGROUND: Venous thromboembolism (VTE) is a common medical condition manifested as deep vein thrombosis (DVT) or pulmonary embolism (PE). Few data exist on the total economic burden of DVT and PE. OBJECTIVES: To (1) quantify the economic burden of DVT and PE in direct medical costs and utilization and (2) determine the rates of hospital readmission for DVT and PE. METHODS: Hospital claims containing DVT or PE as a primary or secondary discharge diagnosis during the period February 1998 through June 2004 were identified by retrospective analysis using the Integrated Health Care Information Services (IHCIS) National Managed Care Database. For the cost analysis, we included patients that had been enrolled in a health care plan for a minimum of 30 days prior to and 365 days following the DVT or PE hospitalization. For the readmission analysis, patients were required to have a minimum length of stay of 3 days and a preenrollment of 365 days. We quantified the cost burden to the health plan by examining annual DVT- and PE-related payments made by the health plan to providers for inpatient and outpatient care. RESULTS: Of 5 million plus discharges in the database with dates of service between February 1, 1998, and June 30, 2004, 32,193 (0.64%) had DVT or PE as a primary discharge diagnosis, and 26,159 (0.52%) had DVT or PE as a secondary discharge diagnosis. After application of the inclusion and exclusion criteria, there were 5,348 patients with a primary discharge diagnosis of DVT and 4,593 patients with a secondary discharge diagnosis of DVT. For PE, 2,984 patients had a primary discharge diagnosis, and 1,119 had a secondary discharge diagnosis. The hospital readmission rates within 1 year for the combined diagnoses (DVT or PE) were 5.3% for primary and 14.3% for secondary diagnoses; 44.3% of the PE readmissions occurred within the first 30 days. Within 90 days, 50.7% of DVT readmissions and 58.6% of PE readmissions occurred. Regarding cost for a primary diagnosis, the average total annual provider payments made by a health plan were $10,804 for DVT and $16,644 for PE. For secondary diagnoses, the average total annual costs were $7,594 for DVT and $13,018 for PE. The mean hospital cost per readmission for a recurrent DVT ($11,862) was higher than the mean cost for the initial hospitalization ($9,805, P=0.006), but the mean cost per PE readmission ($14,722) was similar to the mean cost for the initial hospitalization ($14,146, P=0.38). CONCLUSIONS: The economic burden of DVT and PE in direct medical cost is large, due not only to the initial hospitalization event, but also to the high rate of hospital readmission (5%-14%), over half of which occurs within 90 days.

V enous thromboembolism (VTE) is ac ommon medical condition comprising deep vein thrombosis (DVT) and pulmonarye mbolism (PE). VTE is of particular importance in the hospital setting since moret han half the cases of VTE areaccounted for by institutionalization, with 24% of the cases attributable to hospitalization for surgery. 1 In the absence of prophylaxis, the incidence of objectively confirmed, hospital-acquired DVT ranges from 10% to 40% in the medical and general surgical population to as high as 40% to 60% in patients who have undergone orthopedic surgery. 2 Furthermore,

What is already known about this subject
•VTE is acommon medical condition of particular importance in the hospital setting. In patients with major surgery, the diagnosis and treatment of an initial VTE event poses as ignificant economic burden to health careinthe United States.
•The diagnosis and treatment of the initial VTE event incurs costs, but the VTE recurrences and long-term complications of VTE create additional costs. It was found previously that 1i n4 patients who experienced aV TE event during the incident hospital stay had additional VTE-related events requiring hospitalization in the 21 months of follow-up. These events incurred an average health plan cost of $14,957 per event, or $2,101 per patient per year.

What this study adds
•T he total annual health carec ost for aV TE ranged from $7,594 to $16,644, depending on the type of event and whether it was a primaryo rs econdaryd iagnosis. The hospital readmission rates of DVT or PE within 12 months were5 .3% for primarya nd 14.3% for secondarydiagnoses.
•T he recurrent DVT event was associated with 21% greater cost compared with the initial DVT event, but therew as no difference in cost for the recurrent PE event compared with the initial PE event.
•T he use of health plan total medical costs, including outpatient medical and pharmacy in this study,r esulted in higher total costs compared with previous studies that used hospital inpatient costs.
BACKGROUND: Venous thromboembolism (VTE) is acommon medical condition manifested as deep vein thrombosis (DVT) or pulmonaryembolism (PE). Few data exist on the total economic burden of DVT and PE.
OBJECTIVE: To (1) quantify the economic burden of DVT and PE in direct medical costs and utilization and (2) determine the rates of hospital readmission for DVT and PE.
METHODS: Hospital claims containing DVT or PE as aprimaryorsecondary discharge diagnosis during the period February1998 through June 2004 were identified by retrospective analysis using the Integrated Health CareInformation Services (IHCIS) National Managed CareDatabase.For the cost analysis, we included patients that had been enrolled in ahealth careplan for aminimum of 30 days prior to and 365 days following the DVT or PE hospitalization. For the readmission analysis, patients wererequired to have aminimum length of stay of 3days and apreenrollment of 365 days. We quantified the cost burden to the health plan by examining annual DVT-and PE-related payments made by the health plan to providers for inpatient and outpatient care. in patients who have undergone major orthopedic surgery, the mortality rate due to VTE can be as high as 5%, underscoring the veryh igh-risk natureo ft his population. 2 Recent estimates for the incidence of VTE in the United States suggest that VTE occurs, for the first time, in 100 to120 of every100,000 (~0.1%) of the population yearly. 3,4 Few data exist on the overall economic burden of VTE; however,B otteman et al. 5 constructed am odel to assess costeffectiveness of DVT prophylaxis in total hip replacement (THR) in the United States. They estimated the cost of diagnosis and treatment of DVT at $4,159 and PE at $5,567. Other analyses have provided data on the economic burden of VTE via costeffectiveness studies of prophylaxis versus no prophylaxis. 6−8 As tudy of administrative claim records for January1 ,1 997, through March 31, 2004, found that the median annualized medical costs of patients during and after the DVT or PE event were$17,512 and $18,901, respectively. 9 It is also important to note that the economic burden of VTE is not confined to the diagnosis and treatment of the initial event. Previous studies have demonstrated that ahistoryofVTE is astrong independent risk factor for recurrent VTE in medical patients. 10,11 Furthermore, 7% to 14% of patients with aV TE will have ar ecurrent event within 1y ear, 12−15 afi guret hat rises to approximately 30% at 10 years. 15,16 It has been established that, in high-risk surgical patients, the majority of recurrent VTE occurs shortly after the initial event, most frequently in the first 3m onths. 13 These types of readmissions, especially within 30 days of the original hospital discharge, represent am ajor concerno fq uality patient carea th ospitals. Moreover,t he type of recurrent VTE episode appears to be strongly correlated to the initial VTE. For example, DVT accounted for 86% of recurrent VTE after an initial DVT,and PE accounted for 66% of recurrent VTE after an initial PE. 17 In addition to recurrent VTE, other long-term complications include postthrombotic syndrome 18 and pulmonaryhypertension. 19 The extended cost of long-term complications of VTE has been investigated in as mall number of studies. In patients who had undergone THR, the average lifetime costs associated with long-term complications of VTE was $3,069 per patient. 20 Similarly,i nt he study by Botteman et al. 5 ,t he annual cost of long-term events in patients with VTE after THR was $3,798 for DVT and $6,404 for PE. In an analysis of administrative claims from 2l arge U.S. health carep lans, Bullano et al. found during a21-month follow-up of patients who experienced aVTE event that 13.4% of patients experienced an average of 1.26 recurrent VTE events that required hospitalization, with an average cost of $5,736 per event. 21 Although data exist to show that VTE and its sequelae pose ac onsiderable medical problem, little data exist on the absolute cost burden of VTE. The present study thereforeu sed actual health careplan reimbursement costs compiled in alarge managed cared atabase, containing records from across the United States, to investigate the cost burden of not only initial but also hospital readmission for DVT and PE in the general population. The costs associated with ap rimaryd iagnosis of VTE arer elatively clear as being all costs included during that hospitalization. Patients with VTE as asecondarydiagnosis (and thereforew ith comorbidities) represent an interesting group to comparecosts against patients with VTE as aprimarydiagnosis, since not all hospital costs of these patients area ssociated with the VTE event. Therefore, this study also investigated the costs associated with DVT and PE in patients with VTE as asecondary diagnosis.
nn Methods

Data Source
This study was ar etrospective observational cohort analysis utilizing data from the Integrated Health CareI nformation Services (IHCIS) National Managed CareD atabase, which contains claim information from approximately 30 managed careo rganizations and comprises patient records for approximately 25 million patients across the United States, from 1998 to 2005.

Overall Economic Burden of DVT and PE
For the analysis of the economic burden of DVT or PE, patients wereincluded in the analysis if they had DVT and/or PE as the primaryo rs econdaryd ischarge diagnosis, and the hospitalization event occurred between February1 ,1 998, and June 30, 2004. The first hospitalization for DVT or PE during the study period was defined as the index event. Patients wereexcluded if they did not have continuous health carep lan enrollment and continuous pharmacy benefits for am inimum of 30 days prior to and 365 days following the hospitalization for DVT or PE. In addition, patients wereexcluded if they wereaged older than 65 years and weren ot in the Medicarer isk group (i.e., Medicarecoverage with continuous pharmacy benefit from managed careo rganizations). Patient records that weren ot complete according to aprespecified list of required data fields, which included details of membership, hospitalization, outpatient medical, and outpatient pharmacy,w erea lso excluded from the final analysis.

Comparison of Hospital Reimbursement of DVT/PE Readmissions
For the analysis of the economic burden of hospital readmission for DVT or PE, therew ere2a dditional criteria to ensurethat these patients did have atrue DVT or PE event and hospital readmission: (1) patients werer equired to have a minimum hospital length of stay of 3d ays, and (2) patients werea lso required to have am inimum of 365 days wheret hey did not have any DVT or PE hospitalization but had continuous health carep lan enrollment prior to the index hospitalization (initial DVT or PE hospitalization).
Demographic information was collected for all DVT and PE patients separately.T omeasurehospital readmission for DVT or PE, the following data werec ollected for primaryo rs econdary diagnosis of DVT or PE: type of VTE event, time to first recurrent event, and time patterno fr eadmission (monthly percentages of readmission from the first month to 12 months after first discharge). Only reimbursed hospitalization costs were compared for both initial VTE admission and readmission. Outpatient medical and pharmacy costs werenot measured and compared between the initial VTE admission and readmission, leading to patients being treated as outpatients in the emergency room not being included in the costs. In the evaluation of VTE hospital readmission rate, it was required that the initial DVT or PE hospital admission be followed by aD VT or PE hospital readmission within the required time period. In the evaluation of the time patterno fD VT or PE hospital readmission, only mores pecific readmission types arem easured: an initial DVT admission followed by aD VT readmission or an initial PE admission followed by aPEreadmission.

Total Economic Burden of DVT or PE Analysis
To measuret he economic burden of VTE, the following data werec ollected separately for primaryo rs econdaryd iagnosis of DVT or PE: type of VTE event, length of hospital stay,a nd average total annual reimbursement for DVT or PE-related inpatient costs, outpatient medical costs, outpatient procedure costs and outpatient pharmacy costs. In this analysis, VTErelated inpatient and outpatient pharmacy costs wered efined as those incurred through use of aVTE treatment-related drug, namely unfractionated heparin (UFH), al ow-molecular-weight heparin (LMWH: ardeparin, dalteparin, enoxaparin, or tinzaparin), or danaparoid, warfarin, or fondaparinux. VTE-related outpatient procedurecosts weredefined as those incurred through use of aV TE diagnosis and treatment-related procedures (Appendixes Aand B).

Cost Calculations
Costs associated with various measures of resource utilization werer eported in the IHCIS database on the basis of actual reimbursement by the participating health carep lans, and as such, only costs that werer eimbursed by health carep lans are included in this analysis. For inpatient professional services and outpatient services, only the cost associated with aD VT or PE diagnosis was used in the calculation. For outpatient lab procedures and prescription cost, only procedures or drugs related to the diagnosis and management of VTE were used in the cost calculation (Appendixes Aand B).
Patients with DVT or PE as secondaryd ischarge diagnoses werem atched by primaryd iagnosis, and only the portion of hospital facility cost that was attributable to DVT or PE was estimated and used for the total annualized health carecost. The DVT or PE attributable hospital facility cost is defined as the difference of hospital facility cost between the patient cohort with secondarydiagnoses of DVT or PE and acontrol patient cohort. For each member in the DVT or PE patient cohort, up to 3non-DVT or non-PE members weres elected from the database to form the control cohort based on the following matching criteria: same sex and geographical census region, ≤ 5-year age difference, and the same primaryhospital discharge diagnosis (based on International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes).
Data and costs analysis werep erformed using SAS 8.2 software( SAS Institute Inc., Cary, NC). The Student' s t test assuming unequal variances was carried out to test the statistical significance of the difference in the total hospitalization costs between DVT or PE readmission and the initial DVT or PE hospitalization. A P value below 0.05 was considered as statistically significant in this study.
nn Results

Patient Population
Atotal of 14,108 patients met the inclusion criteria of this study (Figure1 ). Of these patients, 5,348 had ap rimaryd iagnosis of DVT in the index hospitalization, 2,984 had aprimarydiagnosis of PE, afurther 5,776 patients had asecondarydiagnosis of DVT and/or PE in the index hospitalization (4,593 DVT,1 ,119 PE alone, and 64 DVT and PE).
Patients with ap rimaryd iagnosis werey ounger (mean age 53.9 years for the DVT-alone group and 52.7 for the PE-alone group) compared with patients with DVT or PE as asecondary diagnosis (mean age 55.5 and 54.6 years, respectively). Patients werep redominantly female and came from an umber of different census regions (Table 1).

Hospital Readmission Rate for DVT or PE as Primary or Secondary Diagnosis
In patients with aDVT or PE as the primarydiagnosis, the rate of hospital readmission for DVT or PE over 1y ear was 5.3%, while readmission was much higher in patients with DVT or PE as asecondarydiagnosis, reaching arate of 14    Medicaregroup could be related to higher costs in patients aged ≥ 70 years. Although average costs weres imilar for age groups up to 70 years, they wereapproximately 25% higher in patients aged ≥ 70 years compared with the whole population (Table 4).

Economic Burden of DVT and PE as Secondary Diagnosis
The proportion of the average total annualized health carec ost of ap atient that was associated with as econdaryd iagnosis of DVT or PE was lower than in patients with aprimarydiagnosis at $7,594 and $13,018, respectively ( Table 2). The cost in both the DVT and PE groups was primarily driven by hospitalization facility costs ($5,118 and $9,906, respectively), followed by hospitalization professional costs, outpatient procedurec osts, and outpatient prescription costs. The cost of ap atient having both DVT and PE in the secondaryd iagnosis was extremely high at $27,909. However,this result must be treated with caution since it was based on alow number of patients. in line with previous estimates. 12,13,15 In ap opulation-based cohort study of 1,719 patients with afi rst episode of DVT or PE, the cumulative percentage of patients with recurrent VTE was 5.2% at 30 days and 8.3% at 90 days. 15 The cost per event of readmission for DVT and PE observed in our study was also similar to that seen in previous smaller study populations. In the cohort study of Bullano et al., 21 ar ecurrent DVT or PE was associated with at otal hospital cost of $11,419 and $11,014, respectively.These results highlight the importance of preventing afi rst episode of DVT or PE, in order to also reduce the cost burden associated with subsequent long-term complications. The level of readmissions for VTE represents the "worst offenders" in readmission, since the patients arecoming back for exactly the same disease that they just left the hospitals for,with ah igh proportion of readmission occurring in the first 30 days or first 90 days. This represents significant issues for the quality of care. The Joint Committion is in the process of developing aV TE prevention and carep erformance measurement initiative that will come out in 2008. The goal for individual hospitals will be to reduce the incidence of first episode DVT and PE as well as the incidence of hospital readmissions for DVT or PE. The use of evidence-based, guideline-mandated prophylaxis and treatments may help to improve the continuum of careand reduce the economic burden of DVT and PE in these hospitals.
The costs of DVT and PE that wereobserved in patients with ap rimaryd iagnosis of DVT or PE werei nl ine with the results seen in other smaller study populations. For example, in orthopedic surgerypatients, the cost difference for the mean inpatient costs compared with patients without aV TE were$ 7,769 for those patients with aD VT and $9,176 with aP E. 22 In as tudy comparing outpatient LMWH with inpatient unfractionated heparin for patients with confirmed DVT,the average inpatient cost of treating DVT was estimated to be $4,696 per hospitalization compared with $1,868 for outpatient treatment. 23 However, in aretrospective analysis in ahealth maintenance organization in New Mexico, the total average cost for patients treated for aD VT in hospital with unfractionated heparin was $11,930. 24 As tudy from 2m anaged careo rganizations, in the southeasternand westernUnited States, reported the total costs for more than 2,000 patients admitted to the hospital with aD VT or PE. It showed that the average cost per DVT event was $7,712 (median $3,131) and $9,566 (median $6,424) for aPEevent. 21 Little data exists, however,o nt he total hospitalization cost of DVT or PE in large real-world studies that are representative of hospitals across the United States. The present study encompasses total annualized cost data from moret han 12,000 patients with DVT or PE from across the United States, and the costs observed areh igher than for many other studies. These higher costs compared with earlier studies may be ar esult of the data we used, including inpatient as well as outpatient payments to providers. Like Bullano et al. 21 we used net payer costs (i.e., after subtraction of member cost), but we used outpatient costs that included pharmacy as well as inpatient hospital costs. We also report the costs associated with as econdaryd iagnosis of DVT or PE, providing an estimate of the relative component that aV TE event has in the total health carec ost of patients presenting with comorbidities. MacDougall et al., in as imilar analysis of administrative claims data for 1997 through the first quarter of 2004, found median annualized medical costs of $17,512 during and after the DVT event and $18,901 during and after the PE event, representing median annualized incremental costs compared with apreevent baseline of $10,285 for DVT patients and $12,520 for PE patients. 9 These median costs areh igher than the mean costs that we found in the present study,w hich may be explained in part by the inclusion of recurrent VTE in the main cost calculations of the previous study reported by MacDougall and colleagues.

Limitations
Foremost among the study limitations is the difficulty in isolating the incremental medical costs associated with VTE since these patients typically have multiple comorbid conditions. For example, Bullano et al. found previously that disease severity is high in these patients, including 59% with ah istoryo fo r The Total Average Hospitalization active malignancy. 21 Second, the index event for patients in this study was hospitalization for either ap rimaryo rs econdary diagnosis of DVT or PE, and as such, this study excludes patients who wereseen in the emergency room, treated, and sent home on an LMWH or other anticoagulation. Therefore, this study would tend to overestimate the per-patient costs for VTE. On the other hand, since some patients with VTE treated in ah ospital outpatient department wereexcluded, the incidence and prevalence of VTE would be underestimated by our methods.
Third, as with all retrospective administrative data analysis studies, therei st he potential bias from missing data since some records areexcluded from the analysis. However,since the sample size is large in the present study,and the missing data are not expected to be missing in asystematic manner,itisunlikely that this will have al arge impact on the results. In the present study,weused adata source that did not disclose the plan names or detail information about the plans. Therei s, therefore, the chance that the results will not be representative of the national averages. We did however estimate the regional differences in the cost of primaryDVT or PE (data not shown), and found that although differences did exist, they werenot significant.
Fourth, in determining the inclusion and exclusion criteria of this study,anumber of assumptions weremade that may have impacted the results. We required patients to be enrolled in a health carep lan beforet he DVT or PE event for ap eriod of 30 days in the calculations of the total cost of DVT or PE, and for 365 days in the calculations of the hospitalization readmission costs.
Fifth, we also required that patients who werereadmitted for DVT or PE had aminimum length of stay of 3days in both the initial and readmission hospitalization. This was ac onservative approach to ensuret hat during both the initial hospitalizations and readmissions, am inimum length of DVT or PE treatments werea dministered. However,m any legitimate DVT or PE patients, such as those who wereadmitted for only 1to2days and then discharged for outpatient LMWH treatments would have been excluded due to this conservative approach, leading to an overestimation of average cost, but an underestimation of total readmissions.
Thereare also anumber of additional complications of DVT that werenot investigated in this article, but which contribute to the total cost burden of the disease, such as post thrombotic syndrome (PTS). PTS was not included due to the fact that there is not universal consensus on using ICD-9-CM code 459.1 (postphlebitic syndrome) to represent PTS. The costs reported hereare thereforelikely to be an underestimate of the total longterm costs associated with afirst DVT.

nn Conclusion
This study has demonstrated the high cost burden of DVT and PE among al arge national managed carep opulation. Furthermore, it shows that readmission for DVT or PE occurs in up to 14.3% of patients, with 27.1% to 44.3% of readmissions within 30 days, and 50.7% to 57.8% occurring within 90 days. Furthermore, DVT readmissions incur a2 1% greater cost than the initial episode. Hospitals have the potential to reduce the national cost burden of VTE and meet new quality initiatives by ensuring that VTE events areprevented via the use of evidencebased, guideline-mandated prophylaxis options in patients identified at risk of VTE.

disclosures
Financial and editorial support for this research was provided by sanofi-aventis and was obtained by author Alex C. Spyropoulos, who is apaid consultant to sanofi-aventis; author Jay Lin is an employee of sanofi-aventis. Spyropoulos served as principal author of the study.Study concept and design, data collection and interpretation, and writing of the manuscript and its revision werethe work of both authors.